Neonatal maternal separation disrupts regulation of sleep and breathing in adult male rats.

Study Objectives: Neonatal maternal separation (NMS) disrupts development of cardiorespiratory regulation. Adult male rats previously subjected to NMS are hypertensive and show a hypoxic ventilatory response greater than that of controls. These results have been obtained in awake or anesthetised animals, and the consequences of NMS on respiratory control during normal sleep are unknown.

Neonatal caffeine treatment does not induce long-term consequences on TrkB receptors or BDNF expression in chemosensory organs of adult rats.

Chronic treatment with caffeine during the neonatal period (neonatal caffeine treatment, NCT, 15mg/kg/day from P3 to P12, oral gavage) has long-lasting consequences on respiratory control development. In adult male (but not female) rats, prior exposure to NCT results in a greater respiratory frequency response to hypoxia. This sex-specific effect of NCT was accompanied by an augmented expression of adenosine A(2A) receptors (A(2A)R) in the carotid body (CB) but not in the nucleus tractus solitarius (NTS).

Altered expression of adenosine A1 and A2A receptors in the carotid body and nucleus tractus solitarius of adult male and female rats following neonatal caffeine treatment.

Neonatal caffeine treatment (adenosine receptor antagonist, 15 mg/kg/day, between postnatal days 3 and 12) affects respiratory patterns in adult male but not female rats as shown by an increase in the respiratory frequency in the early phase of response to hypoxia and an increase in the tidal volume in the late phase of response. Here, we tested the hypothesis that these changes are correlated with modified expression of adenosine receptors in the chemoreflex pathway. Carotid bodies, nucleus tractus solitarii, and superior cervical ganglia were collected from 3-month-old male and female rats that were either naive (not manipulated during the neonatal period) or treated with caffeine (NCT) or water (NWT) between postnatal days 3 and 12 by gavage.

Enhancement of the breathing frequency response to hypoxia by neonatal caffeine treatment in adult male rats: the role of testosterone.

Caffeine is a common treatment for apnea of prematurity. Although relatively safe, little is known about the potential long-term effects of this treatment on respiratory control development. We previously showed that adult male (but not female) rats previously subjected to neonatal caffeine treatment (NCT; 15 mg/kg/day, postnatal days 3-12) show a higher breathing frequency response during the early phase of hypoxic exposure.

Expression of sex-steroid receptors and steroidogenic enzymes in the carotid body of adult and newborn male rats.

This study describes the localization and pattern of expression of estradiol and progesterone receptors as well as key enzymes for steroid synthesis (i.e. P450 side-chain-cleavage--P450scc, and P450 aromatase--P450Aro) in the carotid body (CB) and superior cervical ganglion (SCG) of adult, newborn and late fetal male rats, using immunohistochemistry, Western blot and real-time RT-PCR.

Neonatal maternal separation and early life programming of the hypoxic ventilatory response in rats.

The neonatal period is critical for central nervous system (CNS) development. Recent studies have shown that this basic neurobiological principle also applies to the neural circuits regulating respiratory activity as exposure to excessive or insufficient chemosensory stimuli during early life can have long-lasting consequences on the performance of this vital system. Although the tactile, olfactory, and auditory stimuli that the mother provides to her offspring during the neonatal period are not directly relevant to respiratory homeostasis, they likely contribute to respiratory control development.

Neonatal maternal separation enhances dopamine D(2)-receptor and tyrosine hydroxylase mRNA expression levels in carotid body of rats.

Adult male (but not female) rats previously subjected to neonatal maternal separation (NMS) are hypertensive and show a significant increase (25%) in their hypoxic ventilatory response. To begin investigating the mechanisms involved in this gender-specific disruption in cardiorespiratory regulation, we tested the hypothesis that NMS alters the expression of dopamine D(2)-receptors and tyrosine hydroxylase mRNA in 3 peripheral organs involved in cardio respiratory regulation: the carotid bodies, superior cervical ganglia, and adrenals. Pups subjected to NMS were placed in a temperature- and humidity-controlled incubator 3 h per day for 10 consecutive days (P3-P12).